Chronic administration of harmine elicits antidepressant-like effects and increases BDNF levels in rat hippocampus.

A growing body of evidence has pointed to the ß-carboline harmine as a potential therapeutic target for the treatment of major depression. The present study was aimed to evaluate behavioural and molecular effects of the chronic treatment with harmine and imipramine in rats. To this aim, rats were treated for 14 days once a day with harmine (5, 10 and 15 mg/kg) and imipramine (10, 20 and 30 mg/kg) and then subjected to the forced swimming and open-field tests. Harmine and imipramine, at all doses tested, reduced immobility time of rats compared with the saline group. Imipramine increased the swimming time at 20 and 30 mg/kg and harmine increased swimming time at all doses. The climbing time increased in rats treated with imipramine (10 and 30 mg/kg) and harmine (5 and 10 mg/kg), without affecting spontaneous locomotor activity. Brain-derived neurotrophic factor (BDNF) hippocampal levels were assessed in imipramine and harmine-treated rats by ELISA sandwich assay. Interestingly, chronic administration of harmine at the higher doses (10 and 15 mg/kg), but not imipramine, increased BDNF protein levels in rat hippocampus. Finally, these findings further support the hypothesis that harmine could bring about behavior and molecular effects, similar to antidepressants drugs.

Effects of beta-carboline harmine on behavioral and physiological parameters observed in the chronic mild stress model: further evidence of antidepressant properties.

The chronic mild stress (CMS) model has been used as an animal model of depression which induces anhedonic behavior in rodents. The present study was aimed to evaluate the behavioral and physiological effects of administration of beta-carboline harmine in rats exposed to CMS procedure. To this aim, after 40 days of exposure to CMS procedure, rats were treated with harmine (15 mg/kg/day) for 7 days. In this study, sweet food consumption, adrenal gland weight, adrenocorticotrophin hormone (ACTH) levels, and hippocampal brain-derived-neurotrophic factor (BDNF) protein levels were assessed. Our findings demonstrated that chronic stressful situations induced anhedonia, hypertrophy of adrenal gland weight, increase ACTH circulating levels in rats and increase BDNF protein levels. Interestingly, treatment with harmine reversed anhedonia, the increase of adrenal gland weight, normalized ACTH circulating levels and BDNF protein levels. Finally, these findings further support the hypothesis that harmine could be a new pharmacological tool for the treatment of depression.

Neurochemical and behavioural effects of acute and chronic memantine administration in rats: Further support for NMDA as a new pharmacological target for the treatment of depression?

A growing body of evidence has pointed to the NMDA receptor antagonists as a potential therapeutic target for the treatment of major depression. The present study was aimed to evaluate behavioural and molecular effects of the acute and chronic treatment with memantine and imipramine in rats. To this aim, rats were acutely or chronically for 14 days once a day treated with memantine (5, 10 and 20 mg/kg) and imipramine (10, 20 and 30 mg/kg) and then subjected to the forced swimming and open-field tests. The acute treatment with memantine at all doses and imipramine at doses (20 and 30 mg/kg) reduced immobility time of rats compared to the saline group (p < 0.05), without affecting spontaneous locomotor activity and chronic treatment with memantine and imipramine, at all doses tested, reduced immobility time of rats compared to the saline group (p < 0.05), without affecting spontaneous locomotor activity. Brain-derived neurotrophic factor (BDNF) hippocampal levels were assessed in imipramine- and memantine-treated rats by ELISA sandwich assay. Interesting enough, acute administration, but not chronic administration of memantine at higher dose (20 mg/kg) increased BDNF protein levels in the rat hippocampus (p < 0.05). Finally, these findings further support the hypothesis that NMDA receptor could be a new pharmacological target for the treatment of depression.

Acute harmine administration induces antidepressive-like effects and increases BDNF levels in the rat hippocampus.

Harmine is a beta-carboline alkaloid that inhibits monoamine reuptake systems. Findings point to an antidepressant effect of the compounds that increases the levels of monoamines after monoamine oxidase inhibition. The present study aims to compare the behavioral effects and the BDNF hippocampus levels of acute administration of harmine and imipramine in rats. To this aim, rats were acutely treated with harmine (5, 10 and 15 mg/kg) and imipramine (10, 20 and 30 mg/kg) and animal behavior was assessed in the forced swimming and open-field tests. Afterwards, hippocampal BDNF protein levels were assessed in imipramine- and harmine-treated rats by ELISA-sandwich assay. We observed that harmine at doses of 10 and 15 mg/kg, and imipramine at 20 and 30 mg/kg reduced immobility time, and increased both climbing and swimming time of rats compared to saline group, without affecting locomotor activity. Acute administration of harmine at the higher dose, but not imipramine, increased BDNF protein levels in the rat hippocampus. Finally, these findings further support the hypothesis that harmine could be a new pharmacological target for the treatment of mood disorders.